Background: Sepsis-induced alterations in mitochondrial function contribute to organ dysfunction and mortality. Measuring mitochondrial function in vital organs is neither feasible nor practical, highlighting the need for non-invasive approaches. Mitochondrial function may be reflected in the concentrations of metabolites found in platelets and whole blood (WB) samples. We proposed to use these as alternates to indirectly estimate platelet mitochondrial oxygen consumption rate (mOCR) in sepsis patients. Methods: We determined the relationships between platelet mOCR and metabolites in both platelets and WB, as measured by quantitative1H-NMR metabolomics. The associations were identified by building multiple linear regression models with stepwise forward-backward variable selection. We considered the models to be significant with an ANOVA test (p-value ≤ 0.05) and a positive predicted-R2. Results: The differences in adjusted-R2 and ANOVA p-values (platelet adj-R2: 0.836 (0.0003), 0.711 (0.0004) vs. WB adj-R2: 0.428 (0.0079)) from the significant models indicate the platelet models were more associated with platelet mOCR. Conclusions: Our data suggest there are groups of metabolites in WB (leucine, acetylcarnitine) and platelets (creatine, ADP, glucose, taurine) that are associated with platelet mOCR. Thus, WB and platelet metabolites could be used to estimate platelet mOCR.
Bibliographical noteFunding Information:
This work was supported by funding from the National Institute for General Medical Sciences (NIGMS), K23GM113041 (MAP) and GM111400 (KAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the NIH.
Funding: This work was supported by funding from the National Institute for General Medical Sciences (NIGMS), K23GM113041 (MAP) and GM111400 (KAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the NIH.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Th.
- Mitochondrial function
- Mitochondrial respiration
- Nuclear magnetic resonance spectroscopy